The resounding success of the Human Genome Project (HGP) clearly illustrates how early investments in developing cost-effective methods of biological data acquisition can have tremendous payoffs for the biomedical community. Over the course of a decade, through refinement, parallelization, and automation of established sequencing technologies, the HGP motivated a 100-fold reduction of sequencing costs, from $10 per finished base to $0.10 per finished base. Initially, the relevance and utility of sequencing and sequencing centers in the wake of the HGP was debated. However, now it is clear that the completion of the human genome marks the end-of-the-beginning, rather than the beginning-of-the-end, of the era of sequencing. The list of realized and potential applications for this type of high-throughput sequencing technology is rich and growing. DNA sequencing technology has the potential to significantly and substantially impact health care, both directly by providing diagnostic and prognostic markers for the clinical setting, and indirectly by accelerating the pace of basic and clinical biomedical research.
High-throughput technologies have succeeded by spatially and temporally increasing the amount of information that can be gathered, e.g., through miniaturization or rapid sample processing. The development of the polony technology is an excellent example of spatial compression. The concept of a polony has evolved over time, and in its current form, polonies allow the formation of millions to billions of distinguishable, immobilized, amplified clonal DNA molecules arising from individual DNA or RNA molecules via a single PCR reaction. The fact that polony technology utilizes only a single step to generate billions of “distinct clones” for sequencing leads this technology to replace the complex robotics required to handle the tens of thousands of cloning and PCR reactions that feed conventional high-throughput sequencing. The development of BEAMing technology allows for further spatial compression.